Cobenfy(KarXT)的注意事项和药物相互作用

Cobenfy (KarXT) is an oral capsule formulation consisting of xanomeline (a muscarinic receptor agonist) and trospiumchloride (a muscarinic receptor antagonist).

Cobenfy (KarXT) Precautions

1. Risk of urinary retention

(1) Risk description: May cause urinary retention. Older patients, those with bladder outlet obstruction (such as benign prostatic hyperplasia (BPH)), or patients with incomplete bladder emptying are at higher risk.

(2) Measures: Monitor symptoms such as difficulty in urinating, thinning of urine stream, and feeling of incomplete urination during medication. It is contraindicated for those with a history of urinary retention. Symptoms should prompt consideration of dose reduction, discontinuation, or urological evaluation.

2. Effects on liver function and contraindications

(1) Risk description: It is contraindicated in patients with moderate to severe hepatic insufficiency. It is also not recommended for patients with mild hepatic insufficiency, because the plasma concentration of xanomeline will significantly increase, increasing the risk of adverse reactions.

(2) Measures: Clinical monitoring of liver enzyme and bilirubin levels is required before medication and during treatment. If signs of severe liver damage such as jaundice and itching occur, the drug should be discontinued immediately.

3. Risk of biliary tract disease

(1) Risk description: Cobenfy may cause transient biliary obstruction, leading to an increase in liver enzymes. The risk is increased for patients with active biliary tract disease such as symptomatic gallstones.

(2) Measures: Not recommended for such patients. Patients with dyspepsia, nausea, vomiting, or epigastric pain should be evaluated for biliary disease and possible pancreatitis.

The pictures come from public channels (such as the official website of the FDA, the official website of the original drug manufacturer, etc.) and are for reference only.

4. Decreased gastrointestinal motility

(1) Risk description: The component trospiumchloride may reduce gastrointestinal motility.

(2) Measures: It is prohibited for those with gastrointestinal obstruction diseases (such as gastric retention). Use with caution in patients with ulcerative colitis, intestinal asthenia, or myasthenia gravis.

5. Risk of angioedema

(1) Risk description: Although rare, angioedema of the face, lips, tongue, and throat may occur and may be life-threatening.

(2) Measures: Once signs of laryngeal edema occur, the medication should be discontinued immediately and emergency medical assistance should be sought. It is contraindicated for those allergic to trospiumchloride.

6. Narrow-angle glaucoma

(1) Risk description: Its anticholinergic effect may cause mydriasis and induce acute narrow-angle glaucoma attacks.

(2) Measures: It is contraindicated in patients with untreated narrow-angle glaucoma. In patients with anatomically narrow angles, use only when the benefits outweigh the risks and with close monitoring.

7. Increased heart rate

(1) Risk description: Cobenfy can cause increased heart rate.

(2) Measures: Heart rate should be monitored before medication and during treatment.

8. Central nervous system effects

(1) Risk description: May cause dizziness, confusion, hallucinations, drowsiness and other central anticholinergic effects.

(2) Measures: It is recommended that patients avoid driving or operating heavy machinery until the effects of the drug are clear. If symptoms occur, dose reduction or discontinuation should be considered.

Cobenfy (KarXT) drug interactions

1. Strong CYP2D6 inhibitors

(1) Impact: Such as paroxetine, fluoxetine, etc., will inhibit the metabolism of xanomeline and increase its blood concentration, thereby increasing the risk of Cobenfy-related adverse reactions.

(2). Recommendation: Adverse reactions should be closely monitored when used together.

2. Drugs actively secreted by renal tubules

(1) Impact: Such as metformin. Trospiumchloride is excreted through this pathway, and coadministration may affect each other's plasma concentrations due to competition for excretion channels.

(2). Recommendation: The adverse reactions of Cobenfy and combined drugs should be monitored when used together.

3. CYP3A4 or P-glycoprotein substrates

(1) Impact: Xanomeline may temporarily inhibit CYP3A4 and P-glycoprotein locally in the intestine, thereby increasing the absorption of the corresponding substrate drugs taken orally (such as certain antiarrhythmic drugs, immunosuppressants).

(2). Recommendation: These substrate drugs should be monitored for increased adverse reactions when used together.

4. Other anticholinergic drugs

(1) Effects: Combined use with other anticholinergic drugs (such as drugs to treat urinary incontinence or allergies) may enhance anticholinergic adverse reactions such as dry mouth and constipation.

(2). Recommendation: Avoid combined use, or closely monitor for anticholinergic side effects.

Cobenfy (KarXT) medication for special groups

1. Elderly patients

The recommended starting dose is 50mg/20mg, twice a day. Slower dose adjustments are recommended, with the maximum recommended dose being 100 mg/20 mg twice daily.

2. Patients with renal insufficiency

(1), mild insufficiency (eGFR60 to <90mL/min): conventional dosage can be used.

(2), Moderate to severe insufficiency (eGFR<60mL/min): Not recommended. Because the clearance of trospiumchloride is reduced and the plasma concentration is increased, the risk of anticholinergic adverse reactions will be significantly increased.

3. Patients with liver insufficiency

(1) Mild insufficiency (Child-Pugh A grade): Not recommended.

(2), moderate to severe insufficiency (Child-Pugh level B and C): disabled.

4. Pregnancy and lactation women

(1) Pregnancy: There are no human data. It should be used after weighing the benefits and risks, and pregnant women are advised to join the Pregnancy Exposure Register.

(2) Lactation period: It is unclear whether the drug is secreted with human milk. The benefits of breastfeeding to the infant, the mother's treatment needs, and the potential risks of the drug to the infant should be comprehensively considered.

5. Pediatric patients

The safety and effectiveness have not been established and it is not suitable for children.